Influence of the type of initial precipitating injury and at what age it occurs on course and outcome in patients with temporal lobe seizures

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✓ The type of initial precipitating injury and the age at which it occurred in 20 patients with nonlesional temporal lobe epilepsy (TLE) were related to clinical features, presurgical neuroimaging, quantified hippocampal pathologies, and seizure outcomes. Clinical data, neuroimaging records, and seizure outcomes were abstracted from medical records and confirmed with patient and family contacts. Hippocampal neuron losses and mossy fiber reactive synaptogenesis were quantified independently. Results showed that the type of initial precipitating injury and the patient's age at which it occurred were related to the clinicopathological features of TLE. An initial precipitating injury occurred in 18 patients (90%), all of whom had mesial temporal sclerosis (MTS). Patients with a prolonged initial seizure or a nonseizure initial precipitating injury before age 5 years were significantly more likely to have unilateral hippocampal atrophy (p < 0.05) shown on magnetic resonance (MR) imaging, and had significantly greater inner molecular layer mossy fiber puncta densities (p < 0.001) than patients with nonprolonged childhood initial precipitating injuries and/or seizures after age 5 years. Furthermore, nonseizure injuries in patients before age 5 years had significantly longer latent periods (p < 0.05), and the patients did not respond to surgical treatment as well as other MTS patients. Those with an initial precipitating injury after age 5 years had MTS but showed significantly less inner molecular layer mossy fiber sprouting (p < 0.05) than patients whose injuries appeared before age 5 years. Patients without an initial precipitating injury (idiopathic TLE) had significantly fewer neuron losses (p < 0.05) and inner molecular layer mossy fiber puncta densities (p < 0.05) and had worse outcomes following en bloc temporal lobectomy compared to patients with MTS who had experienced initial precipitating injuries. Patients with unilateral hippocampal abnormalities on MR imaging did not show significant differences in neuron losses or aberrant mossy fiber puncta densities compared to patients without asymmetry. These results support the hypothesis that the type of initial precipitating injury and the age at which the injury occurred initiates and influences the pathophysiological process that eventually develops into MTS. These data support the notion that the pathophysiology of hippocampal damage and mossy fiber sprouting after an initial precipitating injury may be a progressive process.

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Address reprint requests to: Gary W. Mathern, M.D., Division of Neurosurgery, Reed Neurological Research Center, Room 2144, UCLA Center for Health Sciences, Los Angeles, California 90024–1769.

© AANS, except where prohibited by US copyright law.

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    Graph showing a comparison of the onset of chronic mesial temporal lobe epilepsy in three groups of patients with different types of initial precipitating injuries that occurred prior to 5 years of age. Individual patients are shown by the open symbols and the mean and standard error of the mean are illustrated by the solid circle and bars. Nonseizure initial precipitating injuries (Group A; open circles) had the longest average latent period with a mean of 207 ± 59 months. Prolonged seizure initial precipitating injuries (Group B; open triangles) had a mean latent period of 133 ± 38 months. Nonprolonged initial precipitating injuries (Group C; open boxes) had the shortest latent periods with a mean of 58 ± 31 months. The mean lengths of the latent periods were significantly different between the three initial precipitating injury groups (p < 0.05; Table 2). Notice that half (eight of 16) of the patients experienced onset of their habitual temporal lobe epilepsy (TLE) before 10 years of age (data points shown below the dashed line).

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    Graph showing a comparison of the amount of inner molecular layer (IML) mossy fiber (MF) puncta densities in patients with significant childhood initial precipitating injuries (Groups A and B) compared to patients with nonprolonged initial precipitating injuries (Group C), older initial precipitating injuries (Group D), and idiopathic temporal lobe epilepsy (TLE) (Group E). The average densities (± standard error of the mean) of IML MF puncta for Groups A and B were 17.9 ± 2.9 puncta/10 µm2 and the average densities for the other TLE patients were 5.2 ± 2.0 puncta/10 µm2 (see solid circles for means and standard error of the mean bars). The difference of the means between these two categories was statistically significant (p < 0.001; Student's t-test).

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